Keratometry is measurement of the refractive power of the cornea. The refractive power of an optical surface or combination of optical surfaces is measured in Diopters (D), defined as the inverse of the focal length of the surface or combination measured in meters. Under the assumption that the corneal epithelial and endothelial surfaces are spherical, formulas for calculating the total corneal refractive power are as provided, e.g., in FIG. 2. Accurately calculating the total refractive power may utilize the radii of curvature of both the anterior and posterior surfaces. However, before tomographic techniques became available, the dominant technology for keratometry was corneal topography, which could only measure the anterior surface curvature. If it is assumed that the ratio of the anterior to posterior curvature is invariant, one can obtain a reasonably accurate approximation to the total corneal power (mean keratometric power) from the anterior surface alone by use of an empirically determined “keratometric refractive index,” K. Calculation of corneal refractive power by measurement of the anterior segment radius of curvature over its central 3 mm and use of the keratometric index is the current clinical standard of care. This method has been reported to achieve ˜0.25D accuracy, which is also the standard resolution of eyeglass prescriptions. Tang, M., Li, Y., Avila, M. and Huang, D. Measuring total corneal power before and after laser in situ keratomileusis with high-speed optical coherence tomography. J Cataract Refract Surg, 2006, 32(11), 1843-1850; Koch, D., Foulks, G., Moran, C. and Wakil, J. The Corneal EyeSys System: accuracy analysis and reproducibility of first-generation prototype. Refract Corneal Surg., 1989, 5, 424-429.
The keratometric index method of calculating corneal refractive index is invalid if the assumption of a constant ratio between anterior and posterior corneal curvatures is altered, as occurs after laser refractive surgery. In this case, direct measurement of both corneal surfaces may be necessary. An error in estimation of the axial sag of the corneal anterior surface (defined in FIG. 2 for the posterior surface) of approximately 40 μm at 1.5 mm radius from the optic axis may lead to 0.25D error; any tomographic technique should have at least this much accuracy to be competitive with topography.
Laser refractive surgery (LRS) is a popular elective procedure to help individuals reduce dependence on corrective eyewear. In the United States alone, over 7 million people have already received some form of LRS (LASIK, PRK, and other variants) making LRS one of the most commonly performed of all outpatient surgeries. It is estimated that an additional 700,000 people per year in the U.S. will continue to undergo the LASIK procedure to eliminate their need for glasses or contacts. American Society of Cataract and Refractive Surgery. ASCRS to Participate In and Co-Fund Study on Post-LASIK Quality of Life with U.S. Food and Drug Administration [press release]. 2008). LRS has typically been performed on adult individuals 20 to 40 years old. These millions of individuals have enjoyed close to 20/20 uncorrected visual acuity on average after LRS. Alio J L, M. O., Ortiz D, Perez-Santonja J J, Artola A, Ayala M J, Garcia M J, de Luna G C. Ten-Year Follow-Up of Laser In-Situ Keratomileusis for Myopia up to −10 Diopters. Am J Ophthal, 2008, 145, 46-54; Schallhorn S C, F. A., Huang D, Boxer Wachler B S, Trattler W B, Tanzer D J, Majmudar P A, Sugar A. Wavefront Guided LASIK for the Correction of Primary Myopia and Astigmatism: A Report by the American Academy of Ophthalmology. Ophthalmology, 2008, 115, 1249-1261. However, as all people age into late adulthood, vision invariably deteriorates from age related formation of cataracts, requiring cataract surgery for the restoration of functional vision. Based on a longitudinal study from 1995 to 2002, the estimated annual rate of cataract surgery for individuals older than 62 was 5.3%. Williams A, S. F., Lee P P. Longitudinal rates of cataract surgery. Arch Ophthalmol 2006, 124, 1308-1314. Thus, a projected 370,000 LRS patients will eventually require cataract surgery in at least one eye with a continuing need of about 37,000 per year after those initial patients.
Excimer laser refractive surgery ablates the anterior cornea to achieve a desired refractive correction for the patient. This alters the normal relationship between the anterior and posterior corneal curvatures critical to reflection based topography. Because accurate measurements of corneal power contribute to the proper selection of intraocular lenses needed after cataract surgery, patients who have had laser refractive surgery and subsequently underwent cataract surgery have had unanticipated and undesirable refractive outcomes. Seitz B, L. A., Nguyen N, Kus M, Kuchle M. Underestimation of Intraocular Lens Power for Cataract Surgery after Myopic Photorefractive Keratectomy. Ophthalmology, 1999, 106, 693-702. There continues to be no consensus method to overcome this limitation in accurately measuring corneal power after laser refractive surgery, and surgeons currently warn all these post-laser refractive surgery patients of potential “refractive surprises” after cataract surgery.
In cataract surgery, an artificial intraocular lens (IOL) is implanted to replace the refractive power lost from the removal of the natural lens (cataract). After modern cataract surgery, patients expect to be spectacle independent in part because of the accuracy in predicting the refractive power needed in the IOL. The predicted refractive power, however, depends critically on accurate measurements of the patient's total corneal refractive power (Pt; see FIG. 2). Physically, this parameter depends upon the curvature of the anterior (epithelial) and posterior (endothelial) surfaces of the cornea, as well as the indices of refraction of the intervening media (which are well known). Currently, the most widely used instruments to measure Pt are based on corneal topography, which estimate the refractive power of the cornea from measurements of the curvature of the front surface only. Assumptions are made regarding the refractive contribution of the posterior corneal surface. Klyce, S. Computer-assisted corneal topography. High-resolution graphic presentation and analysis of keratoscopy. Invest Ophthalmol Vis Sci, 1984, 25, 1426-1435. This approach provides satisfactory outcomes for patients with normal corneas, which have a predictable relationship between their front and back curvature. However, this assumption has proven flawed for the first patients who had LRS, subsequently underwent cataract surgery, and had unsatisfactory outcomes. Seitz B, L. A., Nguyen N, Kus M, Kuchle M. Underestimation of Intraocular Lens Power for Cataract Surgery after Myopic Photorefractive Keratectomy. Ophthalmology, 1999, 106, 693-702.
Since its introduction in the early 1990's, optical coherence tomography (OCT) has emerged as a promising imaging modality for micrometer-scale noninvasive imaging in biological and biomedical applications. Its relatively low cost and real-time, in vivo capabilities have fueled the investigation of this technique for applications in retinal and anterior segment imaging in ophthalmology (e.g., to detect retinal pathologies), early cancer detection and staging in the skin, gastrointestinal, and genitourinary tracts, as well as for ultra-high resolution imaging of entire animals in embryology and developmental biology.
Conventional OCT systems are essentially range-gated low-coherence interferometers that have been configured for characterization of the scattering properties of biological and other samples. By measuring singly backscattered light as a function of depth, OCT fills a valuable niche in imaging of tissue ultrastructure, and provides subsurface imaging with high spatial resolution (˜1-10 μm) in three dimensions and high sensitivity (>110 dB) in vivo with no contact needed between the probe and the tissue. OCT is based on the one-dimensional technique of optical coherence domain reflectometry (OCDR), also called optical low-coherence reflectometry (OLCR). See Youngquist, R. C., S. Carr, and D. E. N. Davies, Optical Coherence Domain Reflectometry: A New Optical Evaluation Technique. Opt. Lett., 1987. 12: p. 158; Takada, K., et al., New measurement system for fault location in optical waveguide devices based on an interferometric technique. Applied Optics, 1987. 26(9): p. 1603-1606; and Danielson, B. L. and C. D. Whittenberg, Guided-wave Reflectometry with Micrometer Resolution. Applied Optics, 1987. 26(14): p. 2836-2842. In some instances of time-domain OCT, depth in the sample is gated by low coherence interferometry. The sample is placed in the sample arm of a Michelson interferometer, and a scanning optical delay line is located in the reference arm.
The time-domain approach used in conventional OCT has been used in supporting biological and medical applications. An alternate approach involves acquiring as a function of optical wavenumber the interferometric signal generated by mixing sample light with reference light at a fixed group delay. Two methods have been developed which employ this Fourier domain (FD) approach. The first is generally referred to as Spectral-domain OCT (SDOCT). SDOCT uses a broadband light source and achieves spectral discrimination with a dispersive spectrometer in the detector arm. The second is generally referred to as swept-source OCT (SSOCT). SSOCT time-encodes wavenumber by rapidly tuning a narrowband source through a broad optical bandwidth. Both of these techniques can provide improvements in SNR of up to 15-20 dB when compared to time-domain OCT, because SDOCT and SSOCT capture the complex reflectivity profile (the magnitude of which is generally referred to as the “A-scan” data or depth-resolved sample reflectivity profile) in parallel. This is in contrast to time-domain OCT, where destructive interference is employed to isolate the interferometric signal from only one depth at a time as the reference delay is scanned.
Tomographic corneal imaging methods offer the ability to overcome the assumptions regarding the posterior curvature by directly measuring the posterior curvature. Three commercial clinical modalities are currently available: a slit-scanner based method (Bausch & Lomb Orbscan®), a time-domain based OCT (Carl Zeiss Meditec Visante®), and a rotating Scheimpflug photography based method (Oculus Pentacam®). The slit-scanner calculates the posterior surface mathematically from the front surface (Cairns G, M. C. Orbscan computerized topography: attributes, applications, and limitations. J Cataract Refract Surg, 2005, 31, 205-220), but there are questions regarding its ability to accurately represent the posterior surface. Donnenfeld, E. Discussion of article by Seitz B, Torres F, Langenbucher A, et al. Ophthalmology, 2001, 108, 673. The time-domain OCT instrument does not currently derive curvature information from its images. Because of these limitations and others, neither the slit-scanner nor time-domain OCT is generally used in clinical practice for quantitative evaluation of corneal curvature. The rotating Scheimpflug device takes 25 or 50 full diameter, radial pictures of the cornea and then reconstructs the anterior and posterior corneal surfaces from those photos. This device is used clinically for examining corneal curvature and deriving corneal power, though there is debate regarding the sufficiency of photographic resolution to accurately determine these parameters. None of these approaches appear capable of meeting the rapidly oncoming demand of millions of LRS patients who chose an elective procedure to obtain 20/20 vision and will now expect the same after modern cataract surgery.
Current clinical and research SDOCT systems generally feature about 5 μm axial resolution. Although this resolution is theoretically sufficient to calculate corneal refractive power with approximately 0.25D accuracy independent of the assumptions upon which corneal topography depend. However, conventional OCT imaging faces the additional technical hurdle that cross-sectional images are built up sequentially rather than simultaneously such that each sectional image is built up as the focused beam is scanned across the corneal surface. Despite utilization of a forehead rest in clinical SDOCT systems, it is difficult to immobilize the patient's head to better than about 10-100 μm during the 0.05 seconds required for acquisition of each standard SDOCT B-scan. Thus, as a sequential image is acquired, patient motion may corrupt the true profile of the corneal surfaces sufficiently to degrade the corneal power calculation beyond an acceptable level. Indeed, one OCT study published which quantified keratometric accuracy reported about 0.75D accuracy using moderate-speed OCT (2 kHz A-scan rate) alone. Tang, M., Li, Y., Avila, M. and Huang, D. Measuring total corneal power before and after laser in situ keratomileusis with high-speed optical coherence tomography. J Cataract Refract Surg, 2006, 32(11), 1843-1850.